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High fat diet exacerbates early psoriatic skin inflammation independent of obesity: Saturated fatty acids as key players.

High fat diet exacerbates early psoriatic skin inflammation independent of obesity: Saturated fatty acids as key players.
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Herbert D, Franz S, Popkova Y, Anderegg U, Schiller J, Schwede K, Lorz A, Simon JC, Saalbach A,


Herbert D, Franz S, Popkova Y, Anderegg U, Schiller J, Schwede K, Lorz A, Simon JC, Saalbach A, (click to view)

Herbert D, Franz S, Popkova Y, Anderegg U, Schiller J, Schwede K, Lorz A, Simon JC, Saalbach A,

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The Journal of investigative dermatology 2018 03 29() pii S0022-202X(18)31858-X
Abstract

In obesity, hypertrophic adipocytes secret high amounts of adipocytokines resulting in low-grade inflammation- amplified by infiltrating pro-inflammatory macrophages, oxidative stress, hypoxia and lipolysis. It is known, that these chronic pro-inflammatory conditions support the development of type II diabetes and cardio vascular diseases, while mechanisms of obesity-related exacerbation of inflammatory skin disorders like psoriasis are unclear. In this study, we uncover nutritional saturated fatty acids (SFAs) as major risk factors for the amplification of skin inflammation, independent of obesity-related parameters, like fat mass extension, adipocytokines and glucose homeostasis. Correlation analyses in a cohort of psoriasis vulgaris patients revealed free fatty acid (FFA)-serum-levels as the only obesity-associated parameter affecting disease severity. Studies in high fat diet-induced obese mice with psoriasiform inflammation confirmed this critical role of FFAs. Importantly, an increase of FFAs in healthy, lean mice alone was sufficient to induce an exacerbation of psoriasiform inflammation. In particular, SFAs sensitize myeloid cells to an increased inflammatory response in answer to pro-inflammatory stimuli which in turn augments the activation of keratinocytes. Consequently, reduction of nutritional SFAs alone diminished the psoriatic phenotype in obese mice. Thus, our findings may open new perspectives for adjuvant dietary measures accompanying anti-inflammatory psoriasis therapies in lean and obese patients.

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